In this project a new methodology for heterocyclic synthesis will be introduced which can be classified as a new variant of aza-Robinson annulation. The key synthetic protocol that will constitute the basis for all the proposed synthetic schemes in this proposal features a tandem Michael addition-Dieckmann condensation process between amidines and dimethyl acetylenedicarboxylate (DMAD). The resulting highly functionalized 5-membered nitrogen heterocycles, specifically 4-pyrrolin-3-ones, will serve as key precursors of a wide variety of alkaloids possessing important biological activities. Some of these compounds include 2-acyltetramic acids, pyrrolizidines, indolizidines, piperazines, pyrroloindoles, pyrrolopyridines, pyrrolobenzodiazepines and macrocyclic diamino lactams. The potential therapeutic properties associated with the aforementioned substance classes include, among others, antibacterial, anticarcinogenic, antiviral, HIV inhibitory, analgesic, antimalarial and hypotensive activities. The proposed synthetic plan in each instance is based on some significant preliminary results, and the key chemical transformation reactions featuring the "aza-Robinson" products include hydrolytic cleavage of the vinylogous amide moiety leading to tetramic acids carrying the proper functionality akin to the natural targets, singlet oxygenations that give rise to macrocylic lactams via 4-oxazolidinone intermediates, medium ring bicyclic diaza alkaloids such as piperazines and pyrrolobenzodiazepines through intramolecular reductive amination, Dieckmann type condensations for 5-and 6-membered ring annulation, intramolecular Heck coupling and photocycloadditions, Diels-Alder reactions with inverse electron demand for benzannelations, and hetero-Diels-Alder reactions for pyrrolopyridine synthesis.